Additional Analysis of the Data from the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) (NEI Research Grant for Secondary Data Analysis (R21)) Abstract The proposed project will utilize the comprehensive dataset from the Comparison of Age-related Macular Degeneration (AMD) Treatments Trials (CATT), a multi-center non-inferiority clinical trial, sponsored by the National Eye Institute, to assess the efficacy and safety of ranibizumab (Lucentis) and bevacizumab (Avastin) when treated monthly or PRN (pro re nata). The specific aims of this proposal do not include the major goals of the CATT Study, which were already accomplished. Instead, the proposed project involves additional secondary analysis of the CATT dataset to address the following important new aims: (1) To describe the response pattern of visual acuity over time during the 2 years of treatment, and to determine whether the short-term response of visual acuity (after 1 or 3 injections) predicts the long-term (2 years) visual acuity response. (2) To describe the morphologic changes captured by OCT and fluorescein angiography over time during 2 years of treatment, and to evaluate whether the morphologic responses at 3 months predict the long-term morphologic responses at 2 years. (3) To assess the associations between vision and morphologic changes from anti- VEGF treatment at 2 years. (4) To describe treatment patterns and identify the prognostic factors associated with a low number of treatments in patients treated PRN for 2 years. (5) To assess genotype-phenotype associations with respect to the morphologic features and severity of neovascular AMD at presentation. (6) To evaluate the association of anticoagulation medications with retinal hemorrhage in patients with neovascular AMD. The CATT dataset is a unique resource to further evaluate the effects of Lucentis and Avastin on visual and morphologic changes, to elucidate the association between visual and morphologic responses, and to determine the factors (genetic and systemic drug exposure) that may be associated with features of neovascular AMD at presentation. The analyses of the CATT dataset will provide useful information to the treating ophthalmologists and their patients on what to expect from treatments, and to help monitor and optimize the treatment of the neovascular AMD by personalized medicine. The very large sample size (N=1185), high quality of the dataset, as well as the rich experience and high productivity of the investigators along with the full supports of the CATT Research Group, support the feasibility and likelihood of high yield of the proposed project.